The retina is supplied with oxygen by two separate vascular systems, the choroidal or outer retinal circulation, and the inner retinal circulation (1). Adequate oxygen supply is critical for normal functioning of the retina. The high oxygen requirements of the retina for proper function and the unique structure required for light to reach the photoreceptors make it vulnerable to vascular diseases (2).
Hypoxia plays a role in the onset and progression of various retinal vascular diseases that can cause of irreversible vision loss, including diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration (3-5).
Advancements in technologies including retinal oximetry, phosphorescence lifetime imaging, and Doppler optical coherence tomography (OCT) have provided a greater understanding of vascular oxygen supply and metabolism in the retina. Retinal oximetry measures vascular oxygen tension in inner retinal (6-9) and choroidal vasculature (10) based on hemoglobin oxygen saturation. Phosphorescence lifetime imaging measures oxygen levels using an oxygen sensitive agent that is quenched by oxygen allowing for vascular pO2 levels to be quantified (11). Doppler OCT measures retinal blood flow, which can be used to derive retinal oxygen metabolic measurements (12). However, known methods and systems are unable to detect retinal hypoxia in vivo. Instead, current methods and systems rely on dissection and immunostaining in order to identify hypoxia in the retina. This makes it difficult or impossible to achieve early disease detection, monitoring of disease progression, and assessment of therapeutic responses in the patient.
Accordingly, there remains a need for probes which enable visualization of hypoxic tissue in the retina and other tissues. Furthermore, there remains a need to develop such probes that can work to identify hypoxic cells in living tissue.